Usefulness of the admission electrocardiogram to predict long-term outcomes after non-ST-elevation acute coronary syndrome (from the FRISC II, ICTUS, and RITA-3 [FIR] Trials)

The aim of this study was to evaluate the independent prognostic value of qualitative and quantitative admission electrocardiographic (ECG) analysis regarding long-term outcomes after non-ST-segment elevation acute coronary syndromes (NSTE-ACS). From the Fragmin and Fast Revascularization During Instability in Coronary Artery Disease (FRISC II), Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS), and Randomized Intervention Trial of Unstable Angina 3 (RITA-3) patient-pooled database, 5,420 patients with NSTE-ACS with qualitative ECG data, of whom 2,901 had quantitative data, were included in this analysis. The main outcome was 5-year cardiovascular death or myocardial infarction. Hazard ratios (HRs) were calculated with Cox regression models, and adjustments were made for established outcome predictors. The additional discriminative value was assessed with the category-less net reclassification improvement and integrated discrimination improvement indexes. In the 5,420 patients, the presence of ST-segment depression (≥1 mm; adjusted HR 1.43, 95% confidence interval [CI] 1.25 to 1.63) and left bundle branch block (adjusted HR 1.64, 95% CI 1.18 to 2.28) were independently associated with long-term cardiovascular death or myocardial infarction. Risk increases were short and long term. On quantitative ECG analysis, cumulative ST-segment depression (≥5 mm; adjusted HR 1.34, 95% CI 1.05 to 1.70), the presence of left bundle branch block (adjusted HR 2.15, 95% CI 1.36 to 3.40) or ≥6 leads with inverse T waves (adjusted HR 1.22, 95% CI 0.97 to 1.55) was independently associated with long-term outcomes. No interaction was observed with treatment strategy. No improvements in net reclassification improvement and integrated discrimination improvement were observed after the addition of quantitative characteristics to a model including qualitative characteristics. In conclusion, in the FRISC II, ICTUS, and RITA-3 NSTE-ACS patient-pooled data set, admission ECG characteristics provided long-term prognostic value for cardiovascular death or myocardial infarction. Quantitative ECG characteristics provided no incremental discrimination compared to qualitative data.     

High-sensitivity C-reactive protein predicts adverse outcomes after non-ST-segment elevation acute coronary syndrome regardless of GRACE risk score,but not after ST-segment elevation myocardial infarction

IntroductionAtherosclerosis is an active process and the inflammatory component appears to be particularly correlated with the development of acute coronary syndromes (ACS). C-reactive protein (CRP) is an acute phase protein that appears in the circulation in response to inflammatory cytokines. The present study investigated the association between high-sensitivity C-reactive protein (hsCRP) on admission and follow-up prognosis after an ACS.MethodsWe included 151 consecutive patients admitted to the coronary care unit with a diagnosis of ACS (47% ST-segment elevation myocardial infarction [STEMI]). The primary endpoint was the combination of cardiac death and myocardial reinfarction during the follow-up period (median 19.8 months, interquartile range 16.3–23.7 months).ResultsThe occurrence of follow-up events was significantly related to admission hsCRP level, which was an excellent predictor of cardiac death and reinfarction during follow-up (HR 1.091, 95% CI 1.014–1.174; p=0.019). Stratifying the population based on type of ACS, adjusted by variables associated with cardiac events in univariate analysis (hsCRP, diabetes, depressed ejection fraction and GRACE risk score), hsCRP proved to be an independent predictor of follow-up outcomes only in non-STEMI patients (HR 1.217, 95% CI: 1.093–1.356, p<0.001), not in STEMI patients. The best cutoff level of hsCRP to predict follow-up outcomes was 1.1 mg/dl, with sensitivity of 77.8% and specificity of 63.2%.ConclusionAlthough the GRACE risk score is routinely used for stratification of patients with ACS, assessment of hsCRP may provide additional prognostic value in the follow-up of non-STEMI patients.     

Comprehensive analysis of intravascular ultrasound and angiographic morphology of culprit lesions between ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndrome

Background

Some plaques lead to ST-segment elevation myocardial infarction (STEMI), whereas others cause non-ST-segment elevation acute coronary syndrome (NSTEACS). We used angiography and intravascular ultrasound (IVUS) to investigate the difference of culprit lesion morphologies in ACS.

Methods

Consecutive 158 ACS patients whose culprit lesions were imaged by preintervention IVUS were enrolled (STEMI = 81; NSTEACS = 77). IVUS and angiographic findings of the culprit lesions, and clinical characteristics were compared between the groups.

Results

There were no significant differences in patients' characteristics except for lower rate of statin use in patients with STEMI (20% vs 44%, p = 0.001). Although angiographic complex culprit morphology (Ambrose classification) and thrombus were more common in STEMI than in NSTEACS (84% vs 62%, p = 0.002; 51% vs 5%, p < 0.0001, respectively), SYNTAX score was lower in STEMI (8.6 ± 5.4 vs 11.5 ± 7.1, p = 0.01). In patients with STEMI, culprit echogenicity was more hypoechoic (64% vs 40%, p = 0.01), and the incidence of plaque rupture, attenuation and “microcalcification” were significantly higher (56% vs 17%, p < 0.0001; 85% vs 69%, p = 0.01; 77% vs 61%, p = 0.04, respectively). Furthermore, the maximum area of ruptured cavity, echolucent zone and arc of microcalcification were significantly greater in STEMI compared with NSTEACS (1.80 ± 0.99 mm² vs 1.13 ± 0.86 mm², p = 0.006; 1.52 ± 0.74 mm² vs 1.21 ± 0.81 mm², p = 0.004; 99.9 ± 54.6° vs 77.4 ± 51.2°, p = 0.01, respectively). Quantitative IVUS analysis showed that vessel and plaque area were significantly larger at minimum lumen area site (16.6 ± 5.4 mm² vs 14.2 ± 5.5 mm², p = 0.003; 13.9 ± 5.1 mm² vs 11.6 ± 5.2 mm², p = 0.003, respectively).

Conclusion

Morphological feature (outward vessel remodeling, plaque buildup and IVUS vulnerability of culprit lesions) might relate to clinical presentation in patients with ACS.     

Comparative early and late outcomes after primary percutaneous coronary intervention in ST-segment elevation and non-ST-segment elevation acute myocardial infarction (from the CADILLAC trial)

We determined the outcomes of patients with acute ST-segment elevation (STE) myocardial infarction (STEMI) and non-STEMI (NSTEMI) after primary percutaneous coronary intervention (PCI). The prognosis after primary PCI in STEMI has been extensively studied and defined. Outcomes of patients who undergo primary PCI for NSTEMI are less well established. In total, 2,082 patients with ongoing chest pain for > 30 minutes consistent with acute MI were randomized to balloon angioplasty versus stenting, each with/without abciximab. Of 1,964 patients, STEMI was present in 1,725 (87.8%) and NSTEMI in 239 (12.2%). Compared with STEMI, those with NSTEMI were more likely to have delayed time-to-hospital arrival (2.4 vs 1.8 hours, p = 0.0002) and increased door-to-balloon time (3.2 vs 1.9 hours, p < 0.0001). Patients with NSTEMI were more likely to have Thrombolysis In Myocardial Infarction grade 3 flow at baseline (37.3% vs 19.4%, p < 0.0001) and higher ejection fraction (58.7% vs 55.8%, p = 0.001), but similar rates of postprocedural Thrombolysis In Myocardial Infarction grade 3 flow. At 1 year, patients with NTEMI had similar mortality (3.4% vs 4.4%, p = 0.40) but higher rates of major adverse cardiac events (24.0% vs 16.6%, p = 0.007) that was driven by more frequent ischemic target vessel revascularization (21.8% vs 11.9%, p <0.0001). In conclusion, patients with acute MI without STE who are treated with primary PCI have marked delays to treatment, similar late mortality, and increased rates of ischemic target vessel revascularization compared with patients with STEMI, despite more favorable angiographic features at presentation and similar reperfusion success. The adverse prognosis of patients with NSTEMI should be recognized and efforts made to decrease reperfusion times.     

Association of a history of systemic hypertension with mortality, thrombotic, and bleeding complications following non-ST-segment elevation acute coronary syndrome

Chronic hypertension is a well established risk factor for the development of cardiovascular disease; however, its prognostic significance after a non-ST-segment elevation acute coronary syndrome remains to be established. Data from 15,414 patients included in six randomized Thrombolysis in Myocardial Infarction (TIMI) trials (TIMI 3B, TIMI 11A, TIMI 11B, TIMI 12, the Orbofiban in Patients With Unstable Coronary Syndromes [OPUS]-TIMI 16, and the Treat Angina With Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy [TACTICS]-TIMI 18) were analyzed. A history of hypertension was present in 10,998 (71.35%) patients; comorbidities and higher TIMI risk scores were more likely in these patients. However, positive troponin and ST-segment deviations were less frequent among hypertensive patients. After multivariate analysis, the history of hypertension was associated with more adverse outcomes, specifically the composite end point of death/myocardial infarction at 30 days and 1 year (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.31-1.81; p<0.001 at 1 year) than in patients without this history. An independent relationship was also observed with mortality (OR 1.70, 95% CI 1.34-2.16; p<0.001 at 1 year), myocardial infarction (OR 1.50, 95% CI 1.23-1.82; p<0.001 at 1 year), recurrent ischemia (OR 1.24, 95% CI 1.11-1.38; p<0.001 at 1 year), and major bleeding (OR 1.45, 95% CI 1.03-2.06; p=0.036 at 30 days). It was concluded that chronic hypertension remains an independent marker for major short- and long-term cardiac adverse outcomes after non-ST-segment elevation acute coronary syndrome.     

Comparison of effectiveness of enoxaparin versus unfractionated heparin to reduce silent and clinically apparent acute myocardial infarction in patients presenting with non-ST-segment elevation acute coronary syndrome

Electrocardiographic (ECG) estimates of myocardial infarct size based on the Selvester ECG score have been shown to predict mortality and left ventricular function after acute myocardial infarction (AMI). This score has also been used to identify not clinically apparent AMI ("silent" AMI) and to determine treatment effect, suggesting it could serve as a clinical trial end point. The objective of this study was to compare the rate of silent AMI as measured by the Selvester QRS score in patients with a non-ST-segment elevation acute coronary syndrome treated with enoxaparin versus intravenous unfractionated heparin who were participating in a continuous ECG monitoring substudy of the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events study (ESSENCE) and INTegrelin and Enoxaparin Randomized Assessment of acute Coronary syndrome Treatment trial (INTERACT). Enoxaparin was associated with a 56% relative risk decrease in silent AMI at 96 hours compared with unfractionated heparin (2.7% vs 6.1% p = 0.03). Similarly, enoxaparin decreased Holter-detected myocardial ischemia compared with unfractionated heparin (18.7% vs 35.9%, p = 0.03). In conclusion, enoxaparin significantly decreased the composite of silent AMI or clinical AMI and death at 1 year (9.3% vs 21%, p = 0.0001).     

Primary coronary angioplasty compared with intravenous thrombolytic therapy for acute myocardial infarction: six-month follow up and analysis of individual patient data from randomized trials

Background Overviews of trials suggest that percutaneous transluminal coronary angioplasty (PTCA) may be more effective than thrombolysis. However, whether these effects are sustained beyond hospital discharge, and the extent to which the results are applicable to a broad cross section of patients and the wider community are unknown. We compared the effectiveness of primary PTCA and thrombolysis in acute myocardial infarction during a 6-month follow-up period.Methods Detailed individual patient data were collected from randomized trials commenced from 1989 to 1996 that compared primary PTCA with thrombolysis. Data were combined to produce estimates of relative reduction in events at 30 days and 6 months for the group and for predefined clinical subgroups. Treatment effects were also assessed in relation to several study-related factors.Results Eleven trials were identified. The mortality rate at 30 days was 4.3% for 1348 patients randomized to undergo PTCA, and 6.9% for 1377 patients assigned to thrombolytic therapy (relative risk [RR] 0.62, 95% CI 0.44-0.86, P = .004). At 6 months, the mortality rate was 6.2% for PTCA and 8.2% for thrombolysis (RR 0.73, 95% CI 0.55-0.98, P = .04). Combined death and reinfarction rates at 30 days were 7.0% for PTCA and 12.9% for thrombolysis, with a sustained effect at 6 months (RR 0.60, 95% CI 0.48-0.75, P < .0001). The risk of hemorrhagic stroke at 30 days was lower in the PTCA group (RR 0.06, 95% CI 0.0-0.50, P = .009). The relative treatment effect did not vary across clinically important subgroups, but the absolute benefit varied according to baseline risk. The relative treatment effect varied across the trials and according to the thrombolytic comparator used, the delay in performing PTCA, and the recruitment rate.Conclusion In the context of these trials, primary PTCA was more effective than thrombolytic therapy in reducing death, reinfarction, and stroke, with the greatest absolute benefit in patients who were at the highest risk. These benefits appear to be sustained for 6 months. The effect of treatment varied significantly across the trials, and this raises issues about how widely the results can be applied. (Am Heart J 2003;145:47-57.)     

Prospective comparison of hemorrhagic complications after treatment with enoxaparin versus unfractionated heparin for unstable angina pectoris or non-ST-segment elevation acute myocardial infarction.

Patients with unstable angina pectoris (UAP) or non-ST-segment elevation acute myocardial infarction (AMI) are at risk of death or recurrent ischemic events, despite receiving aspirin and unfractionated heparin (UFH). This study investigates the effect of the low molecular weight heparin, enoxaparin, on the incidence of hemorrhage and thrombocytopenia in relation to baseline characteristics and subsequent invasive procedures. Rates of hemorrhage and thrombocytopenia were analyzed for UAP or non-ST-segment elevation AMI in patients included in the prospective, randomized, double-blind Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) study. Patients received either enoxaparin or UFH, plus aspirin, for 2 to 8 days. The overall rate of major hemorrhage (at 30 days) was comparable between the 2 groups (6.5% for enoxaparin vs. 7.0% for UFH, p = 0.6). The rate of major hemorrhage while on treatment was slightly higher in the enoxaparin group, but this was not significant (1.1% vs 0.7% for UFH, p = 0.204), as was the rate of major hemorrhage within 48 hours of coronary artery bypass grafting performed within 12 hours of treatment. However, the rate of minor hemorrhage was significantly higher in the enoxaparin group, with the majority being injection-site ecchymoses or hematomas (11.9% vs. 7.2% with UFH, p <0.001). Thrombocytopenia (platelet count <100,000 per mm(3)) occurred mainly in association with coronary bypass surgery, with a similar rate in both groups. Thus, enoxaparin is a well-tolerated alternative to UFH in the management of UAP or non-ST-segment elevation AMI. Despite the more effective antithrombotic effect, which results in fewer ischemic events, enoxaparin is not associated with an increase in the rate of major hemorrhagic complications, and is not significantly associated with thrombocytopenia, but is associated with an increase in minor injection site ecchymosis.     

Long-term outcomes of patients receiving zotarolimus-eluting stents in ST elevation myocardial infarction,non-ST elevation acute coronary syndrome,and stable angina: Data from the Resolute program

Background

Outcome data are limited in patients with ST-segment elevation acute myocardial infarction (STEMI) or other acute coronary syndromes (ACSs) who receive a drug-eluting stent (DES). Data suggest that first generation DES is associated with an increased risk of stent thrombosis when used in STEMI. Whether this observation persists with newer generation DES is unknown. The study objective was to analyze the two-year safety and effectiveness of Resolute™ zotarolimus-eluting stents (R-ZESs) implanted for STEMI, ACS without ST segment elevation (non-STEACS), and stable angina (SA).

Methods

Data from the Resolute program (Resolute All Comers and Resolute International) were pooled and patients with R-ZES implantation were categorized by indication: STEMI (n = 335), non-STEACS (n = 1416), and SA (n = 1260).

Results

Mean age was 59.8 ± 11.3 years (STEMI), 63.8 ± 11.6 (non-STEACS), and 64.9 ± 10.1 (SA). Fewer STEMI patients had diabetes (19.1% vs. 28.5% vs. 29.2%; P < 0.001), prior MI (11.3% vs. 27.2% vs. 29.4%; P < 0.001), or previous revascularization (11.3% vs. 27.9% vs. 37.6%; P < 0.001). Two-year definite/probable stent thrombosis occurred in 2.4% (STEMI), 1.2% (non-STEACS) and 1.1% (SA) of patients with late/very late stent thrombosis (days 31–720) rates of 0.6% (STEMI and non-STEACS) and 0.4% (SA) (P = NS). The two-year mortality rate was 2.1% (STEMI), 4.8% (non-STEACS) and 3.7% (SA) (P = NS). Death or target vessel re-infarction occurred in 3.9% (STEMI), 8.7% (non-STEACS) and 7.3% (SA) (P = 0.012).

Conclusion

R-ZES in STEMI and in other clinical presentations is effective and safe. Long term outcomes are favorable with an extremely rare incidence of late and very late stent thrombosis following R-ZES implantation across indications.     

Impact of metabolic syndrome on myocardial perfusion grade after primary percutaneous coronary intervention in patients with acute ST elevation myocardial infarction

AIMS: Metabolic syndrome with its associated cardiovascular risk factors and prothrombotic, procoagulant and proinflammatory properties and its detrimental effects on coronary microcirculation may play a role in the occurrence of poor myocardial perfusion after primary percutaneous coronary intervention in patients with acute myocardial infarction. Accordingly, this study was designed to evaluate the association between metabolic syndrome and myocardial perfusion grade in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention. MATERIAL AND METHODS: The study population included 283 consecutive patients (229 men, mean age=62+/-8 years) admitted to our hospital with ST-elevation myocardial infarction and who underwent primary percutaneous coronary intervention. Thrombolysis in myocardial infarction (TIMI) myocardial perfusion grade (TMPG) was graded densitometrically on the basis of visual assessment of relative contrast opacification of the myocardial territory subtended by the infarct vessel in relation to epicardial density. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III criteria. Patients were divided into two groups on the basis of the myocardial perfusion grade determined after percutaneous coronary intervention. Group I consisted of 223 patients with good myocardial perfusion (TMPG 2-3) after successful percutaneous coronary intervention and group II of 60 patients with poor myocardial perfusion (TMPG 0-1). RESULTS: The prevalence of metabolic syndrome was found to be significantly higher in patients with poor myocardial perfusion than in those with good myocardial perfusion (40 vs. 20%, respectively, P=0.002). Moreover, we detected an independent association between metabolic syndrome and the occurrence of poor myocardial perfusion grade (adjusted OR=2.54, 95% CI=1.35-4.75, P=0.003). CONCLUSIONS: We have shown, for the first time, a significant association between metabolic syndrome and impaired myocardial perfusion after percutaneous coronary intervention in patients with acute myocardial infarction. This data may partially explain the poor short and long-term outcomes of acute myocardial infarction in patients with metabolic syndrome.     

Comparison of baseline characteristics, management and outcome of patients with non-ST-segment elevation acute coronary syndrome in versus not in clinical trials

Previous studies have questioned the external validity of randomized controlled trial results of acute coronary syndrome (ACS) because of potential selection bias toward healthier patients. We sought to evaluate differences in clinical characteristics and management of patients admitted with non-ST-elevation ACS according to participation in clinical trials over the previous decade. The Canadian ACS I (1999 to 2001), ACS II (2002-2003), GRACE (2004-2007), and CANRACE (2008) were prospective, multicenter registries of patients admitted to hospitals with ACS. We examined 13,556 patients with non-ST-elevation ACS, of whom 1,126 (8.3%) participated in clinical trials. Data were collected on baseline characteristics, medication use at admission and discharge, in-hospital procedures, and in-hospital adverse events. Patients enrolled in clinical trials were younger, more likely to be men, and had fewer co-morbidities. They were significantly more likely to be on several guideline-recommended medications and were significantly more likely to undergo invasive procedures, including coronary angiography, percutaneous coronary intervention, and coronary bypass surgery (all p values <0.001). Unadjusted in-hospital (2.1% vs 0.7%, p = 0.001) and 1-year (8.9% vs 6.3%, p = 0.037) mortality rates were higher in non-enrolled patients. In multivariable analysis, patients who were older, women, had a history of heart failure, and increased creatinine levels on presentation were less likely to be enrolled into clinical trials. In conclusion, significant differences persist in baseline characteristics, treatment, and outcomes between patients enrolled and those not enrolled in clinical trials. Consequently, generalization of ACS clinical trials over the previous decade to the "real-world" patient may remain in question.     

Association of glomerular filtration rate on presentation with subsequent mortality in non-ST-segment elevation acute coronary syndrome; observations in 13,307 patients in five TIMI trials.

AIMS: To determine the association of glomerular filtration rate (GFR) with clinical outcomes in the setting of non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS AND RESULTS: Data were pooled from five NSTE-ACS TIMI trials (TIMI 11A and B, TIMI 12, OPUS-TIMI 16 and TACTICS-TIMI 18) and were available in 13 307 patients. GFR was assessed as a continuous and a categorical variable (normal: > or = 90 mL/min/1.73 m2, n=4952; mildly decreased: 60-89 mL/min/1.73 m2, n=6262; and moderately to severely decreased GFR: <60 mL/min/1.73 m2, n=2093). There was an independent association between decreasing GFR and mortality at 30 days (OR 1.19, 95% CI 1.12-1.27, p<0.001) and at 6 months (OR 1.16, 95% CI 1.11-1.22, p<0.001). The combination of TIMI risk score (TRS) and decreasing GFR provided further mortality risk stratification with highest 30-day and 6-month mortality rates among patients with the lowest GFR who also had a TRS > or = 5 (9.1% and 15.4%, respectively). Decreasing GFR was also independently associated with stroke and recurrent ischaemia at 30-days as well as with major bleeding (p<0.001). CONCLUSION: In the setting of NSTE-ACS, impaired GFR is associated with higher mortality as well as higher rates of thrombotic and major bleeding events, independent of TRS.     

Health-related quality of life after interventional or conservative strategy in patients with unstable angina or non-ST-segment elevation myocardial infarction: one-year results of the third Randomized Intervention Trial of unstable Angina (RITA-3)

OBJECTIVES: We sought to compare the effects of an early interventional strategy (IS) versus a conservative strategy (CS) on health-related quality of life (HRQOL) in patients with non-ST-segment elevation acute coronary syndromes (ACS). BACKGROUND: The third Randomized Intervention Trial of unstable Angina (RITA-3) evaluated early IS (n = 895) versus CS (n = 915). We report one-year results of the RITA-3 trial concerning HRQOL. METHODS: The patients' HRQOL was assessed with the Short Form-36 (SF-36) and Seattle Angina Questionnaire (SAQ) at four-month and one-year follow-up, and the EuroQOL Visual Analogue Scale (EQ-VAS) and EuroQOL 5-Dimensional Classification (EQ-5D) also measured at baseline. Analysis was performed using the two-sample t test and analysis of co-variance. RESULTS: Mean changes from baseline EQ-VAS scores were better for IS than for CS at four months (treatment difference of 3.0, p < 0.001) and one year (2.3, p < 0.01). The EQ-5D utility scores were also higher for IS at four months (treatment difference: 0.036, p < 0.01) and at one year (0.016, p = 0.20). For SF-36, IS scored significantly better at four months for physical function, physical role function, emotional role function, social function, vitality, and general health. The SAQ scores for exertional capacity, anginal stability and frequency, treatment satisfaction, and disease perception were better for IS at four months. These treatment differences were present but attenuated by one-year follow-up. Improvements in HRQOL for IS could be attributed to improvements in anginal symptoms. CONCLUSIONS: In patients with non-ST-segment elevation ACS, an early IS provides greater gains in HRQOL, as compared with CS, mainly due to improvements in angina grade.